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Abstract：
Laminin α2 gene (LAMA2)-related Congenital Muscular Dystrophy (CMD) was distinguished by a defining central nervous system (CNS) abnormality-aberrant white matter signals by MRI-when first described in the 1990s. In the past 25 years, researchers and clinicians have expanded our knowledge of brain involvement in LAMA2-related CMD, also known as Congenital Muscular Dystrophy Type 1A (MDC1A). Neurological changes in MDC1A can be structural, including lissencephaly and agyria, as well as functional, including epilepsy and intellectual disability. Mouse models of MDC1A include both spontaneous and targeted LAMA2 mutations and range from a partial loss of LAMA2 function (e.g., dy2J/dy2J ), to a complete loss of LAMA2 expression (dy 3K/dy 3K). Diverse cellular and molecular changes have been reported in the brains of MDC1A mouse models, including blood-brain barrier dysfunction, altered neuro- and gliogenesis, changes in synaptic plasticity, and decreased myelination, providing mechanistic insight into potential neurological dysfunction in MDC1A. In this review article, we discuss selected studies that illustrate the potential scope and complexity of disturbances in brain development in MDC1A, and as well as highlight mechanistic insights that are emerging from mouse models.
摘要：
层粘连蛋白α2基因（LAMA2）相关的先天性肌营养不良（CMD）在1990年代首次描述时，通过MRI确定了中枢神经系统（CNS）异常的白质信号。在过去的25年里,研究人员和临床医生扩大了我们对LAMA2相关CMD的大脑参与的知识，也称为先天性肌营养不良1A型（MDC1A）。MDC1A的神经系统变化可能是结构性的，包括里脑和阿吉利亚,以及功能，包括癫痫和智力残疾。MDC1A的小鼠模型包括自发和靶向的LAMA2突变，并且范围从LAMA2功能的部分丧失（例如，dy2J/dy2J),完全丧失LAMA2表达(dy3K/dy3K)。在MDC1A小鼠模型的大脑中已经报道了不同的细胞和分子变化，包括血脑屏障功能障碍,神经和神经胶质发生改变，突触可塑性的变化，减少髓鞘形成，提供对MDC1A潜在神经功能障碍的机械洞察。在这篇评论文章中，我们讨论了一些研究，这些研究说明了MDC1A大脑发育障碍的潜在范围和复杂性，以及突出显示从小鼠模型中出现的机械见解。
